Circuitry to Assist with Neural Sensing in an Implantable Stimulator Device in the Presence of Stimulation Artifacts

ABSTRACT

Sense amplifier circuits particularly useful in sensing neural responses in an Implantable Pulse Generator (IPG) are disclosed. The IPG includes a plurality of electrodes, with one selected as a sensing electrode and another selected as a reference to differentially sense the neural response in a manner that subtracts a common mode voltage (e.g., stimulation artifact) from the measurement. The circuits include a differential amplifier which receives the selected electrodes at its inputs, and comparator circuitries to assess each differential amplifier input to determine whether it is of a magnitude that is consistent with the differential amplifier&#39;s input requirements. Based on these determinations, an enable signal is generated which informs whether the output of the differential amplifier validly provides the neural response at any point in time. Further, clamping circuits are connected to the differential amplifier inputs to clamp these inputs in magnitude to prevent the differential amplifier from damage.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a non-provisional of U.S. Provisional Patent Application Ser.No. 62/825,981, filed Mar. 29, 2019, which is incorporated herein byreference in its entirety, and to which priority is claimed.

FIELD OF THE INVENTION

This application relates to Implantable Medical Devices (IMDs), and morespecifically to circuitry to assist with sensing neural signals in animplantable stimulator device.

INTRODUCTION

Implantable neurostimulator devices are devices that generate anddeliver electrical stimuli to body nerves and tissues for the therapy ofvarious biological disorders, such as pacemakers to treat cardiacarrhythmia, defibrillators to treat cardiac fibrillation, cochlearstimulators to treat deafness, retinal stimulators to treat blindness,muscle stimulators to produce coordinated limb movement, spinal cordstimulators to treat chronic pain, cortical and deep brain stimulatorsto treat motor and psychological disorders, and other neural stimulatorsto treat urinary incontinence, sleep apnea, shoulder subluxation, etc.The description that follows will generally focus on the use of theinvention within a Spinal Cord Stimulation (SC S) system, such as thatdisclosed in U.S. Pat. No. 6,516,227. However, the present invention mayfind applicability with any implantable neurostimulator device system.

An SCS system typically includes an Implantable Pulse Generator (IPG) 10shown in FIG. 1. The IPG 10 includes a biocompatible device case 12 thatholds the circuitry and a battery 14 for providing power for the IPG tofunction. The IPG 10 is coupled to tissue-stimulating electrodes 16 viaone or more electrode leads that form an electrode array 17. Forexample, one or more percutaneous leads 15 can be used havingring-shaped or split-ring electrodes 16 carried on a flexible body 18.In another example, a paddle lead 19 provides electrodes 16 positionedon one of its generally flat surfaces. Lead wires 20 within the leadsare coupled to the electrodes 16 and to proximal contacts 21 insertableinto lead connectors 22 fixed in a header 23 on the IPG 10, which headercan comprise an epoxy for example. Once inserted, the proximal contacts21 connect to header contacts 24 within the lead connectors 22, whichare in turn coupled by feedthrough pins 25 through a case feedthrough 26to stimulation circuitry 28 within the case 12.

In the illustrated IPG 10, there are thirty-two electrodes (E1-E32),split between four percutaneous leads 15, or contained on a singlepaddle lead 19, and thus the header 23 may include a 2×2 array ofeight-electrode lead connectors 22. However, the type and number ofleads, and the number of electrodes, in an IPG is application specificand therefore can vary. The conductive case 12 can also comprise anelectrode (Ec). In a SCS application, the electrode lead(s) aretypically implanted in the spinal column proximate to the dura in apatient's spinal cord, preferably spanning left and right of thepatient's spinal column. The proximal contacts 21 are tunneled throughthe patient's tissue to a distant location such as the buttocks wherethe IPG case 12 is implanted, at which point they are coupled to thelead connectors 22. In other IPG examples designed for implantationdirectly at a site requiring stimulation, the IPG can be lead-less,having electrodes 16 instead appearing on the body of the IPG 10 forcontacting the patient's tissue. The IPG lead(s) can be integrated withand permanently connected to the IPG 10 in other solutions. The goal ofSCS therapy is to provide electrical stimulation from the electrodes 16to alleviate a patient's symptoms, such as chronic back pain.

IPG 10 can include an antenna 27 a allowing it to communicatebi-directionally with a number of external devices used to program ormonitor the IPG, such as a hand-held patient controller or a clinician'sprogrammer, as described for example in U.S. Patent ApplicationPublication 2019/0175915. Antenna 27 a as shown comprises a conductivecoil within the case 12, although the coil antenna 27 a can also appearin the header 23. When antenna 27 a is configured as a coil,communication with external devices preferably occurs using near-fieldmagnetic induction. IPG 10 may also include a Radio-Frequency (RF)antenna 27 b. In FIG. 1, RF antenna 27 b is shown within the header 23,but it may also be within the case 12. RF antenna 27 b may comprise apatch, slot, or wire, and may operate as a monopole or dipole. RFantenna 27 b preferably communicates using far-field electromagneticwaves, and may operate in accordance with any number of known RFcommunication standards, such as Bluetooth, Zigbee, MICS, and the like.

Stimulation in IPG 10 is typically provided by pulses each of which mayinclude a number of phases such as 30 a and 30 b, as shown in theexample of FIG. 2A. Stimulation parameters typically include amplitude(current I, although a voltage amplitude V can also be used); frequency(F); pulse width (PW) of the pulses or of its individual phases; theelectrodes 16 selected to provide the stimulation; and the polarity ofsuch selected electrodes, i.e., whether they act as anodes that sourcecurrent to the tissue or cathodes that sink current from the tissue.These and possibly other stimulation parameters taken together comprisea stimulation program that the stimulation circuitry 28 in the IPG 10can execute to provide therapeutic stimulation to a patient.

In the example of FIG. 2A, electrode E4 has been selected as an anode(during its first phase 30 a), and thus provides pulses which source apositive current of amplitude +I to the tissue. Electrode E5 has beenselected as a cathode (again during first phase 30 a), and thus providespulses which sink a corresponding negative current of amplitude −I fromthe tissue. This is an example of bipolar stimulation, in which only twolead-based electrodes are used to provide stimulation to the tissue (oneanode, one cathode). However, more than one electrode may be selected toact as an anode at a given time, and more than one electrode may beselected to act as a cathode at a given time.

IPG 10 as mentioned includes stimulation circuitry 28 to form prescribedstimulation at a patient's tissue. FIG. 3 shows an example ofstimulation circuitry 28, which includes one or more current sourcecircuits 40 _(i) and one or more current sink circuits 42 k. The sourcesand sinks 40 _(i) and 42 _(i) can comprise Digital-to-Analog converters(DACs), and may be referred to as PDACs 40 _(i) and NDACs 42 _(i) inaccordance with the Positive (sourced, anodic) and Negative (sunk,cathodic) currents they respectively issue. In the example shown, aNDAC/PDAC 40 _(i)/42 _(i) pair is dedicated (hardwired) to a particularelectrode node ei 39. Each electrode node ei 39 is connected to anelectrode Ei 16 via a DC-blocking capacitor Ci 38, for the reasonsexplained below. The stimulation circuitry 28 in this example alsosupports selection of the conductive case 12 as an electrode (Ec 12),which case electrode is typically selected for monopolar stimulation.PDACs 40 _(i) and NDACs 42 _(i) can also comprise voltage sources.

Proper control of the PDACs 40 _(i) and NDACs 42 _(i) allows any of theelectrodes 16 to act as anodes or cathodes to create a current through apatient's tissue, R, hopefully with good therapeutic effect. In theexample shown (FIG. 2A), and during the first phase 30 a in whichelectrodes E4 and E5 are selected as an anode and cathode respectively,PDAC 404 and NDAC 425 are activated and digitally programmed to producethe desired current, I, with the correct timing (e.g., in accordancewith the prescribed frequency F and pulse widths PWa). During the secondphase 30 b (PWb), PDAC 405 and NDAC 424 would be activated to reversethe polarity of the current. More than one anode electrode and more thanone cathode electrode may be selected at one time, and thus current canflow through the tissue R between two or more of the electrodes 16.

Power for the stimulation circuitry 28 is provided by a compliancevoltage VH. As described in further detail in U.S. Patent ApplicationPublication 2013/0289665, the compliance voltage VH can be produced by acompliance voltage generator 29, which can comprise a circuit used toboost the battery 14's voltage (Vbat) to a voltage VH sufficient todrive the prescribed current I through the tissue R. The compliancevoltage generator 29 may comprise an inductor-based boost converter asdescribed in the '665 Publication, or can comprise a capacitor-basedcharge pump. Because the resistance of the tissue is variable, VH mayalso be variable, and can be as high as 18 Volts in one example.

Other stimulation circuitries 28 can also be used in the IPG 10. In anexample not shown, a switching matrix can intervene between the one ormore PDACs 40 _(i) and the electrode nodes ei 39, and between the one ormore NDACs 42 _(i) and the electrode nodes. Switching matrices allowsone or more of the PDACs or one or more of the NDACs to be connected toone or more anode or cathode electrode nodes at a given time. Variousexamples of stimulation circuitries can be found in U.S. Pat. Nos.6,181,969, 8,606,362, 8,620,436, and U.S. Patent ApplicationPublications 2018/0071520 and 2019/0083796. Much of the stimulationcircuitry 28 of FIG. 3, including the PDACs 40 _(i) and NDACs 42,, theswitch matrices (if present), and the electrode nodes ei 39 can beintegrated on one or more Application Specific Integrated Circuits(ASICs), as described in U.S. Patent Application Publications2012/0095529, 2012/0092031, and 2012/0095519, which are incorporated byreference. As explained in these references, ASIC(s) may also containother circuitry useful in the IPG 10, such as telemetry circuitry (forinterfacing off chip with telemetry antennas 27 a and/or 27 b), thecompliance voltage generator 29, various measurement circuits, etc.

Also shown in FIG. 3 are DC-blocking capacitors Ci 38 placed in seriesin the electrode current paths between each of the electrode nodes ei 39and the electrodes Ei 16 (including the case electrode Ec 12). TheDC-blocking capacitors 38 act as a safety measure to prevent DC currentinjection into the patient, as could occur for example if there is acircuit fault in the stimulation circuitry 28. The DC-blockingcapacitors 38 are typically provided off-chip (off of the ASIC(s)), andinstead may be provided in or on a circuit board in the IPG 10 used tointegrate its various components, as explained in U.S. PatentApplication Publication 2015/0157861.

Although not shown, circuitry in the IPG 10 including the stimulationcircuitry 28 can also be included in an External Trial Stimulator (ETS)device which is used to mimic operation of the IPG during a trial periodand prior to the IPG 10's implantation. An ETS device is typically usedafter the electrode array 17 has been implanted in the patient. Theproximal ends of the leads in the electrode array 17 pass through anincision in the patient and are connected to the externally-worn ETS,thus allowing the ETS to provide stimulation to the patient during thetrial period. Further details concerning an ETS device are described inU.S. Pat. No. 9,259,574 and U.S. Patent Application Publication2019/0175915.

Referring again to FIG. 2A, the stimulation pulses as shown arebiphasic, with each pulse at each electrode comprising a first phase 30a followed thereafter by a second phase 30 b of opposite polarity.Biphasic pulses are useful to actively recover any charge that might bestored on capacitive elements in the electrode current paths, such asthe DC-blocking capacitors 38, the electrode/tissue interface, or withinthe tissue itself. To recover all charge by the end of the second pulsephase 30 b of each pulse (Vc4=Vc5=0V), the first and second phases 30 aand 30 b are preferably charged balanced at each electrode, with thephases comprising an equal amount of charge but of the oppositepolarity. In the example shown, such charge balancing is achieved byusing the same pulse width (PWa=PWb) and the same amplitude (|+I|=|−I|)for each of the pulse phases 30 a and 30 b. However, the pulse phases 30a and 30 b may also be charged balance if the product of the amplitudeand pulse widths of the two phases 30 a and 30 b are equal, as is known.

FIG. 3 shows that stimulation circuitry 28 can include passive recoveryswitches 41 _(i), which are described further in U.S. Patent ApplicationPublications 2018/0071527 and 2018/0140831. Passive recovery switches 41_(i) may be attached to each of the electrode nodes 39, and are used topassively recover any charge remaining on the DC-blocking capacitors Ci38 after issuance of the second pulse phase 30 b—i.e., to recover chargewithout actively driving a current using the DAC circuitry. Passivecharge recovery can be prudent, because non-idealities in thestimulation circuitry 28 may lead to pulse phases 30 a and 30 b that arenot perfectly charge balanced. Passive charge recovery typically occursduring at least a portion 30 c (FIG. 2A) of the quiet periods betweenthe pulses by closing passive recovery switches 41 _(i). As shown inFIG. 3, the other end of the switches 41 _(i) not coupled to theelectrode nodes 39 are connected to a common reference voltage, which inthis example comprises the voltage of the battery 14, Vbat, althoughanother reference voltage could be used. As explained in the above-citedreferences, passive charge recovery tends to equilibrate the charge onthe DC-blocking capacitors 38 and other capacitive elements by placingthe capacitors in parallel between the reference voltage (Vbat) and thepatient's tissue. Note that passive charge recovery is illustrated assmall exponentially-decaying curves during 30 c in FIG. 2A, which may bepositive or negative depending on whether pulse phase 30 a or 30 b has apredominance of charge at a given electrode.

SUMMARY

An implantable medical device is disclosed, which may comprise: a firstelectrode node coupleable to a first electrode configured to makeelectrical contact with a patient's tissue, and a second electrode nodecoupleable to a second electrode configured to make electrical contactwith the patient's tissue, wherein the first electrode node isconfigured to receive via the first electrode a tissue signal from thepatient's tissue; an amplifier with a first input connected to the firstelectrode node and with a second input connected to the second electrodenode, wherein the amplifier produces an amplifier output indicative ofthe tissue signal; first comparator circuitry configured to receive thefirst input and to generate a first output indicating whether the firstinput meets an input requirement of the amplifier; second comparatorcircuitry configured to receive the second input and to generate asecond output indicating whether the second input meets an inputrequirement of the amplifier; and first logic circuitry configured toreceive the first output and the second output and to generate an enablesignal, wherein the enable signal indicates whether the amplifier outputindicative of the tissue signal is valid or invalid.

In one example, the first and second electrode nodes comprise two of aplurality of electrodes nodes, and wherein the first and secondelectrodes comprise two of a plurality of electrodes, wherein each ofthe plurality of electrode nodes are coupleable to a different one theplurality of electrodes, wherein the plurality of electrodes areconfigured to make electrical contact with the patient's tissue. In oneexample, the implantable medical device further comprises a selectorcircuit configured to select the first and second electrode nodes fromthe plurality of electrode nodes. In one example, the implantablemedical device further comprises stimulation circuitry configured toproduce stimulation in the tissue via selected ones of the plurality ofelectrodes, wherein the tissue signal is generated in the patient'stissue in response to the stimulation. In one example, the secondelectrode comprises a conductive case of the implantable medical device.In one example, the implantable medical device further comprises a lead,wherein the lead comprises the first and second electrodes. In oneexample, a first blocking capacitor intervenes between the firstelectrode node and the first electrode, and wherein a second blockingcapacitor intervenes between the second electrode node and the secondelectrode. In one example, the tissue signal comprises a neuralresponse. In one example, the implantable medical device furthercomprises a first clamping circuit configured to keep a voltage at thefirst input from exceeding a first value, and a second clamping circuitconfigured to keep a voltage at the second input from exceeding thefirst value. In one example, the first clamping circuit is furtherconfigured to keep the voltage at the first input from going below asecond value, and wherein the second clamping circuit is furtherconfigured to keep the voltage at the second input from going below thesecond value. In one example, the implantable medical device furthercomprises a first DC-level shifting circuit configured to set a DCvoltage reference at the first input, and a second DC-level shiftingcircuit configured to set the DC voltage reference at the second input.In one example, the amplifier comprises a first input transistor with afirst control terminal for receiving the first input, and a second inputtransistor with a second control terminal for receiving the secondinput, wherein the first and second input transistors comprise athreshold voltage that must respectively be exceeded at the first andsecond inputs to turn on the first and second transistors. In oneexample, the first comparator circuitry comprises a first comparatorconfigured to indicate at the first output whether a voltage at thefirst input exceeds the threshold voltage, and wherein the secondcomparator circuitry comprises a second comparator configured toindicate at the second output whether a voltage at the second inputexceeds the threshold voltage. In one example, the first comparatorcircuitry comprises: a first comparator configured to indicate whether avoltage at the first input exceeds a first voltage, a second comparatorconfigured to indicate whether the voltage at the first input is below asecond voltage, and second logic circuitry configured to receive theoutputs of the first and second comparators and to generate the firstoutput, wherein the first output indicates whether or not the voltage atthe first input is between the first and second voltages; and whereinthe second comparator circuitry comprises: a third comparator configuredto indicate whether a voltage at the second input exceeds the firstvoltage, a fourth comparator configured to indicate whether the voltageat the second input is below the second voltage, and second logiccircuitry configured to receive the outputs of the third and fourthcomparators and to generate the second output, wherein the second outputindicates whether or not the voltage at the second input is between thefirst and second voltages. In one example, the first voltage comprises athreshold voltage of input transistors in the amplifiers, and whereinthe second voltage comprises a power supply voltage of the amplifier. Inone example, the implantable medical device further comprises controlcircuitry configured to receive the amplifier output indicative of thetissue signal, wherein the control circuitry is programmed with analgorithm configured to analyze the amplifier output, wherein operationof the algorithm is controlled by the enable signal.

An implantable medical device is disclosed, which may comprise: a firstelectrode node coupleable to a first electrode configured to makeelectrical contact with a patient's tissue, wherein the first electrodenode is configured to receive via the first electrode a tissue signalfrom the patient's tissue; an amplifier with a first input connected tothe first electrode node and with a second input connectable to areference voltage, wherein the amplifier produces an amplifier outputindicative of the tissue signal; and comparator circuitry configured toreceive the first input and to generate an enable signal indicatingwhether the first input meets an input requirement of the amplifier,wherein the enable signal indicates whether the amplifier outputindicative of the tissue signal is valid or invalid.

In one example, the first electrode node comprises one of a plurality ofelectrodes nodes, and wherein the first electrode comprises one of aplurality of electrodes, wherein each of the plurality of electrodenodes are coupleable to a different one the plurality of electrodes,wherein the plurality of electrodes are configured to make electricalcontact with the patient's tissue. In one example, the implantablemedical device further comprises a selector circuit configured to selectthe first electrode nodes from the plurality of electrode nodes. In oneexample, the implantable medical device further comprises stimulationcircuitry configured to produce stimulation in the tissue via selectedones of the plurality of electrodes, wherein the tissue signal isgenerated in the patient's tissue in response to the stimulation. In oneexample, the reference voltage comprises a DC voltage. In one example,the implantable medical device further comprises a lead, wherein thelead comprises the first electrode. In one example, a first blockingcapacitor intervenes between the first electrode node and the firstelectrode. In one example, the tissue signal comprises a neuralresponse. In one example, the implantable medical device furthercomprises a clamping circuit configured to keep a voltage at the firstinput from exceeding a first value. In one example, the clamping circuitis further configured to keep the voltage at the first input from goingbelow a second value. In one example, the implantable medical devicefurther comprises a DC-level shifting circuit configured to set a DCvoltage reference at the first input. In one example, the amplifiercomprises a first input transistor with a first control terminal forreceiving the first input, and a second input transistor with a secondcontrol terminal for receiving the second input, wherein the first andsecond input transistors comprise a threshold voltage that mustrespectively be exceeded at the first and second inputs to turn on thefirst and second transistors. In one example, the comparator circuitrycomprises a comparator configured to indicate at enable signal whether avoltage at the first input exceeds the threshold voltage. In oneexample, the comparator circuitry comprises: a first comparatorconfigured to indicate whether a voltage at the first input exceeds afirst voltage, a second comparator configured to indicate whether thevoltage at the first input is below a second voltage, and logiccircuitry configured to receive the outputs of the first and secondcomparators and to generate the enable signal, wherein the enable signalindicates whether or not the voltage at the first input is between thefirst and second voltages. In one example, the first voltage comprises athreshold voltage of input transistors in the amplifiers, and whereinthe second voltage comprises a power supply voltage of the amplifier. Inone example, the implantable medical device further comprises controlcircuitry configured to receive the amplifier output indicative of thetissue signal, wherein the control circuitry is programmed with analgorithm configured to analyze the amplifier output, wherein operationof the algorithm is controlled by the enable signal.

An implantable medical device is disclosed, which may comprise: a firstelectrode node coupleable to a first electrode configured to makeelectrical contact with a patient's tissue, and a second electrode nodecoupleable to a second electrode configured to make electrical contactwith the patient's tissue, wherein the first electrode node isconfigured to receive via the first electrode a tissue signal from thepatient's tissue; an amplifier with a first input connected to the firstelectrode node and with a second input connected to the second electrodenode, wherein the amplifier produces a first amplifier output and asecond amplifier output together comprising a differential amplifieroutput indicative of the tissue signal; comparator circuitry configuredto determine from the first amplifier output a first comparator outputindicating whether the first input meets an input requirement of theamplifier, and determine from the second amplifier output a secondcomparator output indicating whether the second input meets an inputrequirement of the amplifier; and logic circuitry configured to receivethe first comparator output and the second comparator output and togenerate an enable signal, wherein the enable signal indicates whetherthe differential amplifier output indicative of the tissue signal isvalid or invalid.

In one example, the first and second electrode nodes comprise two of aplurality of electrodes nodes, and wherein the first and secondelectrodes comprise two of a plurality of electrodes, wherein each ofthe plurality of electrode nodes are coupleable to a different one theplurality of electrodes, wherein the plurality of electrodes areconfigured to make electrical contact with the patient's tissue. In oneexample, the implantable medical device further comprises a selectorcircuit configured to select the first and second electrode nodes fromthe plurality of electrode nodes. In one example, the implantablemedical device further comprises stimulation circuitry configured toproduce stimulation in the tissue via selected ones of the plurality ofelectrodes, wherein the tissue signal is generated in the patient'stissue in response to the stimulation. In one example, the secondelectrode comprises a conductive case of the implantable medical device.In one example, the implantable medical device further comprises a lead,wherein the lead comprises the first and second electrodes. In oneexample, a first blocking capacitor intervenes between the firstelectrode node and the first electrode, and wherein a second blockingcapacitor intervenes between the second electrode node and the secondelectrode. In one example, the tissue signal comprises a neuralresponse. In one example, the implantable medical device furthercomprises a first clamping circuit configured to keep a voltage at thefirst input from exceeding a first value, and a second clamping circuitconfigured to keep a voltage at the second input from exceeding thefirst value. In one example, the first clamping circuit is furtherconfigured to keep the voltage at the first input from going below asecond value, and wherein the second clamping circuit is furtherconfigured to keep the voltage at the second input from going below thesecond value. In one example, the implantable medical device furthercomprises a first DC-level shifting circuit configured to set a DCvoltage reference at the first input, and a second DC-level shiftingcircuit configured to set the DC voltage reference at the second input.In one example, the amplifier comprises a first input transistor with afirst control terminal for receiving the first input, and a second inputtransistor with a second control terminal for receiving the secondinput, wherein the first and second input transistors comprise athreshold voltage that must respectively be exceeded at the first andsecond inputs to turn on the first and second transistors. In oneexample, the amplifier further comprises a first resistance seriallyconnected between the first input transistor and a power supply voltage,and a second resistance serially connected between the second inputtransistor and the power supply voltage, wherein the first amplifieroutput comprises a node between the first input transistor and the firstresistance, and wherein the second amplifier output comprises a nodebetween the second input transistor and the second resistance. In oneexample, the comparator circuitry comprises: a first comparatorconfigured to indicate whether a voltage at the first differentialoutput is below a first voltage, a second comparator configured toindicate whether a voltage at the second differential output is belowthe first voltage. In one example, the amplifier is powered by a powersupply voltage, and wherein the first voltage is less than the powersupply voltage. In one example, the implantable medical device furthercomprises control circuitry configured to receive the differentialamplifier output indicative of the tissue signal, wherein the controlcircuitry is programmed with an algorithm configured to analyze theamplifier output, wherein operation of the algorithm is controlled bythe enable signal.

An implantable medical device is disclosed, which may comprise: a firstelectrode node coupleable to a first electrode configured to makeelectrical contact with a patient's tissue, wherein the first electrodenode is configured to receive via the first electrode a tissue signalfrom the patient's tissue; an amplifier with a first input connected tothe first electrode node and with a second input connectable to areference voltage, wherein the amplifier produces a first amplifieroutput and a second amplifier output together comprising a differentialamplifier output indicative of the tissue signal; and comparatorcircuitry configured to determine from the first amplifier output anenable signal indicating whether the first input meets an inputrequirement of the amplifier, wherein the enable signal indicateswhether the differential amplifier output indicative of the tissuesignal is valid or invalid.

In one example, the first electrode node comprises one of a plurality ofelectrodes nodes, and wherein the first electrode comprises one of aplurality of electrodes, wherein each of the plurality of electrodenodes are coupleable to a different one the plurality of electrodes,wherein the plurality of electrodes are configured to make electricalcontact with the patient's tissue. In one example, the implantablemedical device further comprises a selector circuit configured to selectthe first electrode nodes from the plurality of electrode nodes. In oneexample, the implantable medical device further comprises stimulationcircuitry configured to produce stimulation in the tissue via selectedones of the plurality of electrodes, wherein the tissue signal isgenerated in the patient's tissue in response to the stimulation. In oneexample, the reference voltage comprises a DC voltage. In one example,the implantable medical device further comprises a lead, wherein thelead comprises the first electrode. In one example, a first blockingcapacitor intervenes between the first electrode node and the firstelectrode. In one example, the tissue signal comprises a neuralresponse. In one example, the implantable medical device furthercomprises a clamping circuit configured to keep a voltage at the firstinput from exceeding a first value. In one example, the clamping circuitis further configured to keep the voltage at the first input from goingbelow a second value. In one example, the implantable medical devicefurther comprises a DC-level shifting circuit configured to set a DCvoltage reference at the first input. In one example, the amplifiercomprises a first input transistor with a first control terminal forreceiving the first input, and a second input transistor with a secondcontrol terminal for receiving the second input, wherein the first andsecond input transistors comprise a threshold voltage that mustrespectively be exceeded at the first and second inputs to turn on thefirst and second transistors. In one example, the amplifier furthercomprises a first resistance serially connected between the first inputtransistor and a power supply voltage, and a second resistance seriallyconnected between the second input transistor and the power supplyvoltage, wherein the first amplifier output comprises a node between thefirst input transistor and the first resistance, and wherein the secondamplifier output comprises a node between the second input transistorand the second resistance. In one example, the comparator circuitrycomprises a comparator configured to indicate whether a voltage at thefirst differential output is below a first voltage. In one example, theamplifier is powered by a power supply voltage, and wherein the firstvoltage is less than the power supply voltage. In one example, theimplantable medical device further comprises control circuitryconfigured to receive the differential amplifier output indicative ofthe tissue signal, wherein the control circuitry is programmed with analgorithm configured to analyze the amplifier output, wherein operationof the algorithm is controlled by the enable signal.

An implantable medical device is disclosed, which may comprise: a firstelectrode node coupleable to a first electrode configured to makeelectrical contact with a patient's tissue, and a second electrode nodecoupleable to a second electrode configured to make electrical contactwith the patient's tissue, wherein the first electrode node isconfigured to receive via the first electrode a tissue signal from thepatient's tissue; an amplifier with a first input connected to the firstelectrode node and with a second input connected to the second electrodenode, wherein the amplifier produces an amplifier output indicative ofthe tissue signal; a first clamping circuit configured to keep a voltageat the first input from exceeding a first value; and a second clampingcircuit configured to keep a voltage at the second input from exceedingthe first value.

In one example, the first clamping circuit is further configured to keepthe voltage at the first input from going below a second value, andwherein the second clamping circuit is further configured to keep thevoltage at the second input from going below the second value. In oneexample, the first and second electrode nodes comprise two of aplurality of electrodes nodes, and wherein the first and secondelectrodes comprise two of a plurality of electrodes, wherein each ofthe plurality of electrode nodes are coupleable to a different one theplurality of electrodes, wherein the plurality of electrodes areconfigured to make electrical contact with the patient's tissue. In oneexample, the implantable medical device further comprises a selectorcircuit configured to select the first and second electrode nodes fromthe plurality of electrode nodes. In one example, the implantablemedical device further comprises stimulation circuitry configured toproduce stimulation in the tissue via selected ones of the plurality ofelectrodes, wherein the tissue signal is generated in the patient'stissue in response to the stimulation. In one example, the secondelectrode comprises a conductive case of the implantable medical device.In one example, the implantable medical device further comprises a lead,wherein the lead comprises the first and second electrodes. In oneexample, a first blocking capacitor intervenes between the firstelectrode node and the first electrode, and wherein a second blockingcapacitor intervenes between the second electrode node and the secondelectrode. In one example, the tissue signal comprises a neuralresponse.

An implantable medical device is disclosed, which may comprise: a firstelectrode node coupleable to a first electrode configured to makeelectrical contact with a patient's tissue, and a second electrode nodecoupleable to a second electrode configured to make electrical contactwith the patient's tissue, wherein the first electrode node isconfigured to receive via the first electrode a tissue signal from thepatient's tissue; an amplifier with a first input connected to the firstelectrode node and with a second input connected to the second electrodenode, wherein the amplifier produces an amplifier output indicative ofthe tissue signal; a first DC-level shifting circuit configured to set aDC voltage reference at the first input; and a second DC-level shiftingcircuit configured to set the DC voltage reference at the second input.

In one example, the first and second electrode nodes comprise two of aplurality of electrodes nodes, and wherein the first and secondelectrodes comprise two of a plurality of electrodes, wherein each ofthe plurality of electrode nodes are coupleable to a different one theplurality of electrodes, wherein the plurality of electrodes areconfigured to make electrical contact with the patient's tissue. In oneexample, the implantable medical device further comprises a selectorcircuit configured to select the first and second electrode nodes fromthe plurality of electrode nodes. In one example, the implantablemedical device further comprises stimulation circuitry configured toproduce stimulation in the tissue via selected ones of the plurality ofelectrodes, wherein the tissue signal is generated in the patient'stissue in response to the stimulation. In one example, the secondelectrode comprises a conductive case of the implantable medical device.In one example, the implantable medical device further comprises a lead,wherein the lead comprises the first and second electrodes. In oneexample, a first blocking capacitor intervenes between the firstelectrode node and the first electrode, and wherein a second blockingcapacitor intervenes between the second electrode node and the secondelectrode. In one example, the tissue signal comprises a neuralresponse.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an Implantable Pulse Generator (IPG), in accordance withthe prior art.

FIGS. 2A and 2B show an example of stimulation pulses producible by theIPG, in accordance with the prior art.

FIG. 3 shows stimulation circuitry useable in the IPG, in accordancewith the prior art.

FIG. 4 shows an improved IPG having neural response sensing, and theability to adjust stimulation dependent on such sensing.

FIGS. 5A-5D shows stimulation producing a neural response, and thesensing of that neural response at at least one electrode of the IPGusing a differential amplifier.

FIGS. 6A and 6B show a first example of a sense amp circuit with adifferential amplifier for sensing a neural response, including a clampcircuit for the inputs of the differential amplifier, comparatorcircuitries for determining if the magnitude of the inputs are too low,and logic circuitry for generating an enable signal informing when theoutput of the differential amplifier is valid.

FIGS. 7A and 7B show a second example of a sense amp circuit similar toFIGS. 6A and 6B, but includes comparator circuitries for determining ifthe magnitude of the inputs are too low or too high.

FIG. 8 shows a third example of a sense amp circuit similar to theabove, including comparator circuities for determining if the outputs ofthe differential amplifier are valid for sensing, and generating anenable signal informing when the output of the differential amplifier isvalid.

FIG. 9 shows a fourth example of a sense amp circuit combining theapproaches of FIGS. 7A and 8.

FIGS. 10A and 10B shows other examples of sense amp circuits used in adifferential sensing mode, in which one of the inputs to thedifferential amplifier is set to a DC voltage.

DETAILED DESCRIPTION

An increasingly interesting development in pulse generator systems, andin Spinal Cord Stimulator (SCS) pulse generator systems specifically, isthe addition of sensing capability to complement the stimulation thatsuch systems provide. For example, and as explained in U.S. PatentApplication Publication 2017/0296823, it can be beneficial to sense aneural response in neural tissue that has received stimulation from anSCS pulse generator. One such neural response is an Evoked CompoundAction Potential (ECAP). An ECAP comprises a cumulative responseprovided by neural fibers that are recruited by the stimulation, andessentially comprises the sum of the action potentials of recruitedfibers when they “fire.” An ECAP is shown in FIG. 4, and comprises anumber of peaks that are conventionally labeled with P for positivepeaks and N for negative peaks, with P1 comprising a first positivepeak, N1 a first negative peak, P2 a second positive peak and so on.Note that not all ECAPs will have the exact shape and number of peaks asillustrated in FIG. 4, because an ECAP's shape is a function of thenumber and types of neural fibers that are recruited and that areinvolved in its conduction. An ECAP is generally a small signal, and mayhave a peak-to-peak amplitude on the order of tens of microVolts to tensof milliVolts.

Also shown in FIG. 4 is circuitry for an IPG 100 (or an ETS) that iscapable of providing stimulation and sensing a resulting ECAP or otherneural response or signal. The IPG 100 includes control circuitry 102,which may comprise a microcontroller for example such as Part NumberMSP430, manufactured by Texas Instruments, which is described in datasheets at http://www.ti.com/lsds/ti/microcontroller/16-bitmsp430/overview.page? DCMP=MCU_other& HQS=msp430, which is incorporatedherein by reference. Other types of controller circuitry may be used inlieu of a microcontroller as well, such as microprocessors, FPGAs, DSPs,or combinations of these, etc. Control circuitry 102 may also be formedin whole or in part in one or more Application Specific IntegratedCircuits (ASICs), such as those described and incorporated earlier.

The IPG 100 also includes stimulation circuitry 28 to producestimulation at the electrodes 16, which may comprise the stimulationcircuitry 28 shown earlier (FIG. 3). A bus 118 provides digital controlsignals from the control circuitry 102 (and possibly from an ECAPalgorithm 124, described below) to one or more PDACs 40 _(i) or NDACs 42_(i) to produce currents or voltages of prescribed amplitudes (I) forthe stimulation pulses, and with the correct timing (PW, f). As notedearlier, the DACs can be powered between a compliance voltage VH andground. As also noted earlier, but not shown in FIG. 4, switch matricescould intervene between the PDACs and the electrode nodes 39, andbetween the NDACs and the electrode nodes, to route their outputs to oneor more of the electrodes, including the conductive case electrode 12(Ec). Control signals for switch matrices, if present, may also becarried by bus 118. Notice that the current paths to the electrodes 16include the DC-blocking capacitors 38 described earlier, which providesafety by preventing the inadvertent supply of DC current to anelectrode and to a patient's tissue. Passive recovery switches 41 _(i)(FIG. 3) could also be present, but are not shown in FIG. 4 forsimplicity.

IPG 100 also includes sensing circuitry 115, and one or more of theelectrodes 16 can be used to sense neural responses such as the ECAPsdescribed earlier. In this regard, each electrode node 39 is furthercoupleable to a sense amp circuit 110. Under control by bus 114, amultiplexer 108 can select one or more electrodes to operate as sensingelectrodes by coupling the electrode(s) to the sense amps circuit 110 ata given time, as explained further below. Although only one multiplexer108 and sense amp circuit 110 is shown in FIG. 4, there could be morethan one. For example, there can be four multiplexer 108/sense ampcircuit 110 pairs each operable within one of four timing channelssupported by the IPG 100 to provide stimulation. The analog waveformcomprising the ECAP is preferably converted to digital signals by one ormore Analog-to-Digital converters (ADC(s)) 112, which may sample thewaveform at 50 kHz for example. The ADC(s) 112 may also reside withinthe control circuitry 102, particularly if the control circuitry 102 hasA/D inputs. Multiplexer 108 can also provide a reference voltage, Vamp,to the sense amp circuit 110, as is useful in a single-ended sensingmode, as explained later with reference to FIGS. 10A and 10B.

So as not to bypass the safety provided by the DC-blocking capacitors38, the input to the sense amp circuitry 110 is preferably taken fromthe electrode nodes 39, and so the DC-blocking capacitors 38 intervenebetween the electrodes 16 where the ECAPs are sensed and the electrodenodes 39. However, because the DC-blocking capacitors 38 will pass ACsignals while blocking DC components, the AC ECAP signal will passthrough the capacitors 38 and is still readily sensed by the sense ampcircuit 110. In other examples, the ECAP may be sensed directly at theelectrodes 16 without passage through intervening capacitors 38.

As shown, an ECAP algorithm 124 is programmed into the control circuitry102 to receive and analyze the digitized ECAPs. One skilled in the artwill understand that the ECAP algorithm 124 can comprise instructionsthat can be stored on non-transitory machine-readable media, such asmagnetic, optical, or solid-state memories within the IPG 100 (e.g.,stored in association with control circuitry 102).

In the example shown in FIG. 4, the ECAP algorithm 124 operates withinthe IPG 100 to determine one or more ECAP features, which may includebut are not limited to:

-   -   a height of any peak (e.g., H_N1) present in the ECAP;    -   a peak-to-peak height between any two peaks (such as H_PtoP from        N1 to P2);    -   a ratio of peak heights (e.g., H_N1/H_P2);    -   a peak width of any peak (e.g., the full width half maximum of a        N1, FWHM_N1);    -   an area under any peak (e.g., A_N1);    -   a total area (A_tot) comprising the area under positive peaks        with the area under negative peaks subtracted or added;    -   a length of any portion of the curve of the ECAP (e.g., the        length of the curve from P1 to N2, L_P1toN2)    -   any time defining the duration of at least a portion of the ECAP        (e.g., the time from P1 to N2, t_P1toN2);    -   a time delay from stimulation to issuance of the ECAP, which is        indicative of the neural conduction speed of the ECAP, which can        be different in different types of neural tissues;    -   any mathematical combination or function of these variables        (e.g., H_N1/FWHM_N1 would generally specify a quality factor of        peak N1).

Once the ECAP algorithm 124 determines one or more of these features, itmay then adjust the stimulation that the IPG 100 provides, for exampleby providing new data to the stimulation circuitry 28 via bus 118. Thisis explained further in U.S. Patent Application Publications2017/0296823 and 2019/0099602, which are incorporated herein byreference in their entireties. In one simple example, the ECAP algorithm124 can review the height of the ECAP (e.g., its peak-to-peak voltage),and in closed loop fashion adjust the amplitude I of the stimulationcurrent to try and maintain the ECAP to a desired value.

FIGS. 5A and 5B show a percutaneous lead 15, and show the stimulationprogram example of FIG. 2A in which electrodes E4 and E5 are used toproduce pulses in a bipolar mode of stimulation, with (during the firstphase 30 a) E4 comprising an anode and E5 a cathode, although otherelectrode arrangements (e.g., tripoles, etc.) could be used as well.Such stimulation produces an electromagnetic (EM) field 130 in a volumeof the patient's tissue around the selected electrodes. Some of theneural fibers within the EM field 130 will be recruited and fire,particularly those proximate to the cathodic electrode E5. Hopefully thesum of the neural fibers firing will mask signals indicative of pain inan SCS application, thus providing the desired therapy. The recruitedneural fibers in sum produce an ECAP, which can travel both rostrallytoward the brain and caudally away from the brain. The ECAP passesthrough the spinal cord by neural conduction with a speed which isdependent on the neural fibers involved in the conduction. In oneexample, the ECAP may move at a speed of about 5 cm/1 ms.

The ECAP is preferably sensed differentially using two electrodes, andFIGS. 5A and 5B show different examples. In FIG. 5A, a single electrodeE8 on the lead 15 is used for sensing (S+), with another signal beingused as a reference (S−). In this example, the sensing reference S−comprises a more distant electrode in the electrode array 17 or (asshown) the case electrode Ec. (However, reference S− could also comprisea fixed voltage provided by the IPG 100, such as ground, in which casesensing would be said to be single-ended instead of differential). InFIG. 5B, two lead-based electrodes are used for sensing, with suchelectrodes either being adjacent or at least relatively close to oneanother. Specifically, in this example, electrode E8 is again used forsensing (S+), with adjacent electrode E9 providing the reference (S−).This could also be flipped, with E8 providing the reference (S−) forsensing at electrode E9 (S+). Sensing a given ECAP at differentelectrodes can allow the ECAP algorithm 124 to understand the timedifference between the arrival of the ECAP at each of the electrodes. Ifthe distance x between the electrodes is known, the ECAP algorithm 124can then compute speed of the ECAP. As noted above, ECAP speed isindicative of the neural fibers involved in neural recruitment andconduction, which can be interesting to know in its own right, and whichmay be useful to the ECAP algorithm 124 in adjusting the stimulationprovided by the stimulation circuitry 28.

FIG. 5C shows waveforms for the stimulation program, as well as thesignal that would appear in the tissue at sensing electrode E8 (S+). Aswell as including the ECAP to be sensed, the signal at the sensingelectrode S+ also includes a stimulation artifact 134. The stimulationartifact 134 comprises a voltage that is formed in the tissue as aresult of the stimulation, i.e., as result of the EM field 130. Asdescribed in U.S. Patent Application Publication 2019/0299006, which isincorporated herein by reference in its entirety, the PDACs and NDACsused to form the currents in the tissue have high output impedances.This can cause the voltage in the tissue to vary between ground and thecompliance voltage VH used to power the DACs, which as noted earlier canbe a high voltage (e.g., as high as 18V). The magnitude of thestimulation artifact 134 at a given sensing electrode S+ or itsreference S− can therefore be high (e.g., several Volts), andsignificantly higher than the magnitude of the ECAP. The magnitude ofthe stimulation artifact 134 at the sensing electrodes S+ and S− isdependent on many factors. For example, the stimulation artifact 134will be larger if the sensing electrodes are closer to the electrodesused to provide the stimulation (E4, E5). The stimulation artifact 134is also generally larger during the provision of the pulses, although itmay still be present even after the pulse (i.e., the last phase 30 b ofthe pulse) has ceased due to the capacitive nature of the tissue, whichkeeps the electric field 130 from dissipating immediately.

The relatively large-signal background stimulation artifact 134 can makeresolution and sensing of the small-signal ECAP difficult at the senseamp circuit 110. To ameliorate this concern, it can be beneficial to usea sensing electrode S+ that is far away from the stimulating electrodes.See, e.g., U.S. patent application Ser. No. 16/661,549, filed Oct. 23,2019, which is incorporated herein by reference in its entirety. Thiscan be beneficial because the stimulation artifact 134 would be smallerat a distant sensing electrode, and because the ECAP would pass adistant sensing electrode at a later time when the stimulation artifact134 might have dissipated (e.g., ECAP2 in FIG. 5C). However, using adistant sensing electrode is not always possible or practical. For one,the electrode array 17 may simply not be large enough, and therefore noelectrode may be suitably far enough away from the stimulatingelectrodes to ideally operate as the sensing electrode. Likewise, themagnitude of the ECAP also diminishes as distance from the stimulatingelectrodes increases, and therefore while the stimulation artifact 134would be smaller at a more distant sensing electrode, so too would theECAP, again making sensing difficult.

Sensing the ECAP may also be easier during periods when the stimulationartifact 134 is smaller. For example, and as shown in FIG. 5C, thestimulation artifact 134 can be relatively large during the time thatthe pulse (i.e., its phases) is issuing (30 a and 30 b), making sensingof ECAP (e.g., ECAP1) particularly difficult during that time. It maythen be desirable to sense the ECAP after the pulse has ceased, when thestimulation artifact is smaller and decreasing (e.g., ECAP2). However,sensing the ECAP after cessation of the pulse is not always possible,depending on various factors. For example, if the sensing electrode S+is close to the stimulating electrodes, if the pulse width of the pulse(or its phases) is relatively long, or if the speed of the ECAP isrelatively fast, it cannot always be possible to sense the ECAP aftercessation of the pulse. Also, it may be necessary to use passive chargerecovery after the cessation of the pulse. As noted earlier, passivecharge recovery involves shorting the electrode nodes 39 to a referencevoltage (e.g., Vbat) through passive charger recovery switches 41 _(i)(FIG. 3). ECAP sensing may be difficult when the passive charge recoveryswitches are closed, as the electrode node 39 carrying the ECAP to thesense amp circuit 110 would be shorted to the reference voltage duringthis time. It may therefore be necessary in certain circumstances tosense the ECAP during the provision of the pulse or one of its phases.

Differential sensing, in which the reference electrode S− is alsoexposed to the tissue and therefore to the stimulation artifact 134 toat least some degree, can assist ECAP resolution, and is shown in FIG.5D. A simple example of sense amp circuit 110 is shown, which includes adifferential amplifier 111. Also shown is a simple example of thecircuitry within the differential amplifier 111, although it should benoted that many different differential amplifier circuits exist and canbe used as well. Understand that the multiplexer 108 (FIG. 4) or otherselector circuit could be present between the electrode nodes 39 and thedifferential amplifier 111, but this not shown in FIG. 5D forsimplicity.

Sensing electrode S+ and sensing reference electrode S− are coupledthrough the DC-blocking capacitors 38 (if used) to derive signals X+ andX− at the electrode nodes 39 that are presented to the positive andnegative inputs of the differential amplifier 111. As noted earlier,signals X+ and X− will be largely the same as S+ and S− present at theselected sensing electrodes, but with DC signal components removed. X+and X− are provided to the gates (control terminals) of transistors M+and M− in the differential amplifier 111. The drains of the transistorsM+ and M− are connected to outputs D+ and D−, which in turn are coupledto the amplifier's power supply voltage Vdd via resistances R+ and R−.The sources of the transistors M+ and M− are connected to ground as theother power supply voltage through a common bias transistor Mb, whichsets the total current Ib that, in sum, can pass through each of thelegs (I+, I−) of the differential amplifier. Resistances R+ and R− areequal and are represented as simple resistors, although active devices(e.g., PMOS transistor) could also be used. The output of the amplifier111, Vo, equals the difference in the voltages at outputs D+ and D−,which in turn is influenced by the difference in the signals present atX+ and X−. Signals X+ and X−, if different, will turn transistors M+ andM− on to different degrees, thus causing different currents I+ and I− toflow through each leg. This produces different voltage drops across theresistances R+ and R−, and thus different voltages at D+ and D−. Inshort, Vo=D+−D−=A(X+−X−), where A is the gain of the amplifier.

If the stimulation artifact 134 is present at both the sensing electrodeS+ and reference electrode S−, the differential amplifier 111 willsubtract the stimulation artifact as a common mode voltage from theoutput, ideally leaving only the ECAP to be sensed at the output. Notethat the magnitude of the stimulation artifact 134 may not be exactlythe same at sensing electrodes S+ and S−, which is not surprising aseach is necessarily located at a different distance from the stimulatingelectrodes, and so common mode removal of the stimulation artifact maybe not be perfect. Nevertheless, differential sensing allows thestimulation artifact 134 to be removed to at least some degree, makingit easier to resolve the small-signal ECAP.

Differential sensing as illustrated in FIG. 5D can however beproblematic, in particular because of limitations inherent in thedifferential amplifier 111. As noted earlier, the stimulation artifact134 can vary by several Volts in the tissue, and X+ and X− may exceedthe input requirements of the differential amplifier 111. Note that thedifferential amplifier 111 is powered by a power supply Vdd. This powersupply Vdd is typically on the order of 3.3V or so, thus allowing thedifferential amplifier 111 to be simply and conveniently made fromstandard low voltage transistors such as M+ and M−. While thedifferential amplifier 111 can still work if X+ and X− are slightlyhigher than Vdd, amplifier operation would eventually be compromised ifX+ and X− are significantly higher, which is entirely possible dependingon the circumstances. Further, if X+ and X− are too high, the inputtransistors M+ and M− can become damaged, rendering the differentialamplifier 111 non-functional.

X+ and X− can also be too low to allow for accurate sensing. In thisregard, the input transistors M+ and M− are in this example NMOStransistors which have inherent gate threshold voltages (e.g.,Vtt=0.7V), meaning that X+ and X− at the gate of these transistors mustbe above Vtt to turn the transistors on and to produce appreciablecurrents I+ and I− in each leg. If X+ or X− are lower than Vtt, I+ andI− will not flow to a significant degree. This means that the ECAPpresent in X+ may not be detected, or that the common mode voltageprovided by the stimulation artifact 134 will not be properly subtractedby the differential amplifier 111.

In short, inputs X+ and X− in the sense amp circuitry 110 should behigher than the threshold voltages of the input transistors M+ and M−,and (preferably) below the differential amplifier 111′s power supplyvoltage Vdd. Further, because X+ and X− can be high enough to damage thedifferential amplifier 111, further considerations in the sense ampcircuit 110 are desired to ensure that this does not happen.

FIGS. 6A and 6B describe a first example of a sense amp circuit 200designed to address these concerns, and includes additional circuitry tosupplement the differential amplifier 111. As well as providing the ECAPsignal to the control circuitry 102/ECAP algorithm 124 for analysis atoutput 145, the sense amp circuit 200 provides one or more enablesignals (e.g., En) to inform the ECAP algorithm 124 when X+ and X− areof a magnitude such that the ECAP algorithm 124 can consider the ECAP atoutput 145 to be valid. As explained further below, enable signal En isissued as valid when X+ and X− are of a magnitude that is consistentwith the input requirements of the differential amplifier 111.

As a preliminary matter, note that differential amplifier 111 mayprovide its output to various processing circuits 147 prior topresentation to the control circuitry 102 and the ECAP algorithm 124.For example, the differential amplifier 111's differential output (D+and D−) may be provided to the inputs of another differential amplifier146, and to still further differential amplifiers in series, etc. Thiscan be helpful in increasing the gain of the detected ECAP signal,because the gains of each amplifier stage will multiply (A1*A2, etc.). Afollower circuit or buffer could also be used in series as part of theprocessing circuitry 147 between the differential amplifier 111 and theADC 112 but such stages are not shown. Further, the processing circuitry147 may include a Low Pass Filter (LPF) 148 to remove high-frequencycomponents in the ECAP signal that are not of interest, or that areinconsistent with the rate at which the ADC 112 will sample the signal.In one example, the LFP 148 removes frequency components of 25 kHz orhigher. Processing circuitry 147 may be considered part of the controlcircuitry 102.

To prevent damage to or improper operation of the differential amplifier111 (i.e., the first differential amplifier in series), inputs X+ and X−are provided with clamping circuits 142+ and 142− respectively. In theexample shown, clamping circuit 142+ comprises a serial connection ofdiodes 144 a and 144 b which are forward biased between a low clampreference voltage reference (Vcl) and a high clamp reference voltage(Vch), and with signal X+ connected to a node between the diodes. Vcland Vch preferably comprise ground and the power supply voltage Vdd(e.g., 3.3V). In this example, it is assumed that the diodes 144 a and114 b have a forward biased threshold voltage (Vtd) of 0.6V. Diode 144 awould conduct (turn on) if the voltage at X+ is less than −0.6 Volts.Because such conductance is of very low resistance, X+ is effectivelyclamped to a minimum of Vmin=−0.6 Volts. If it is assumed that Vdd=3.3V, diode 144 b would conduct if X+ is greater than 3.9V Volts, whichwould clamp X+ to a maximum of Vmax=3.9V. If the voltage at X+ is at orbetween −0.6 and 3.9 Volts, neither diode 144 a nor 144 b in clampingcircuit 142+ would conduct. Clamping circuit 142− is similar, butconnects to signal X−, and so similarly clamps X− to a voltage at orbetween −0.6 and 3.9 Volts.

To summarize, clamping circuits 142+ and 142− allow X+ and X− to pass tothe inputs of the differential amplifier 111 without clamping if theyare between −0.6 and 3.9 Volts, but otherwise clamps voltages on thesesignals from exceeding 3.9 Volts or from being lower than −0.6V. Thisprotects the differential amplifier 111. As noted above, if the inputsX+ or X− are significantly higher than the power supply voltage Vdd, theinput transistors M+ and M− may become damaged. Further, if inputs X+ orX− are too low, the amplifier 111 may also not function properly,because the sources of drains of those transistors M+ and M− may startto leak to the substrate of those transistors.

Modifications may be made to the clamping circuits 142+ and 142− toadjust the window of permissible voltages at which clamping does notoccur. For example, Vcl and Vch could be generated by their owngenerator circuits (similar to 141, discussed below) to produce uniquevalues different from ground and Vdd. More than two diodes may also beused in series; for example, four diodes could be used in series, and ifX+ or X− is connected between the middle two, this would expand thewindow to voltages from −1.2V (ground −2 Vtd) to 4.5V (Vdd+2 Vtd). Zenerdiodes could also be used, which could break down and thus clamp X+ orX− at specified reverse bias voltages.

The sense amp circuit 200 further includes DC-level shifting circuits143+ and 143− to set signals X+ and X− to a DC voltage referenceconsistent with the input requirements for the differential amplifier111. As discussed above, the differential amplifier 111 can only operatereliably if signals X+ and X− are of a magnitude that causes current I+and I− to flow in each leg of the amplifier. In this regard, to sensethe small-signal ECAP, X+ and X− should be higher than the thresholdvoltage of the amplifier's input transistors M+ and M− (e.g., greaterthan Vtt=0.7 V). It is further preferred that X+ and X− not exceed thepower supply voltage Vdd of the differential amplifier (e.g., Vdd=3.3V)for proper amplifier operation. Accordingly, signals provided to thedifferential amplifier 111 are preferably referenced with respect to aDC voltage reference within this operating range. This reference couldcomprise ½ Vdd (e.g., 1.65 V), which comprises a midpoint between Vddand ground. More preferably, the DC voltage reference could comprise ½(Vdd−Vtt)+ Vtt (e.g., 2.0 V), as this value would be midpoint within theoperating range 0.7V and 3.3V, and thus allow X+ and X− to symmetricallyswing +/−1.3V from the reference while still providing an inputmagnitude suitable to operate the differential amplifier 111.

The magnitude of the DC voltage reference can be set at signals X+ andX− via DC-level shifting circuits 143+ and 143−. While such circuits cantake different forms, in the example shown they comprise a resistorladder, comprising resistors Ra and Rb in series biased between Vdd andground, with signals X+ and X− connected to nodes between the resistors.This sets the DC voltage reference of both X+ and X− toRa/(Ra+Rb)*(Vdd-ground). Thus by setting the values of Ra and Rbappropriately, the DC voltage reference can be set to any desired valuebetween Vdd and ground, such as 2.0 V. AC signals then coupling to X+and X− through the capacitors 38 (such as the ECAP and/or thestimulation artifact 134) will then be referenced to (and ride on topoff) this DC voltage reference. As a general matter, this allows thedifferential amplifier 111 to be affected by the ECAP at X+, because thesuperposition of the ECAP and the DC voltage reference will cause achange in current I+. Preferably, Ra and Rb are large resistances, such1 MegaOhm or higher.

Also present in sense amp circuitry 200 are comparator circuitries 150+and 150−, which are connected to signals X+ and X− respectively. Thegoal of comparator circuitries 150+ and 150− are to respectivelydetermine whether signals X+ and X− are of a reliable magnitude to senseECAPs, and to indicate the same to the ECAP algorithm 124 via generationof an enable signal, En. Even though a DC voltage reference (e.g., 2.0V) is established at X+ and X− by DC-level shifting circuits 143+ and143−, the AC nature of the stimulation artifact 134 can cause largevariations from this baseline. The enable signal En may change from timeto time depending on the voltages at X+ and X−, and thus there may betimes when the enable signal indicates to the ECAP algorithm 124 thatoutput 145 is providing reliable ECAP data that is valid to assess atoutput 145 (‘0’), and times when it indicates that output 145 is notproducing reliable ECAP data and can be ignored (‘1’).

Comparator circuitry 150+ includes a comparator 154+ which receives X+at its negative input, and a low sense reference voltage Vsl at itspositive input. In one example, Vsl is set by a voltage generator 141 toa value that ensures that X+ is high enough to properly turn ontransistor M+ in the differential amplifier 111. Many different types ofgenerator circuits can be used to produce Vsl, including bandgapgenerator circuits, but FIG. 6A shows use of a simple resistor in serieswith an adjustable current source to set Vsl to the correct value. Inone example, Vsl equals (or could be slightly higher than) the thresholdvoltage of M+, i.e., Vsl=Vtt=0.7V. If X+ is higher than Vsl, thecomparator 154+ will output a ‘0’ at signal Y+ ; by contrast, if X+ islower than Vsl, the comparator will output a ‘1’ at signal Y+.Comparator circuitry 150− is similar in construction and operation tocomparator circuity 150+, and includes a comparator 154− to compare X−to Vsl and to determine when X− is suitably high (Y−=‘0’) or too low(Y−=‘1’).

While signals Y+ and Y− could be sent to control circuitry 102/ECAPalgorithm 124 to operate as separate enable signals, in a preferredexample, these signals are provided to logic circuitry such as an ORgate 158, which produces a single enable signal, En. Thus, if either Y+or Y− equals ‘1’, meaning that either X+ or X− is too low to properlyoperate the differential amplifier, En=‘1’. The ECAP algorithm 124 cantherefore ignore ECAPs reported at output 145 in this circumstance, andinstead only consider as valid ECAPs reported when En=‘0’, where Y+ andY− are both ‘0’. FIG. 6B summarizes operation of the sense amp circuit200, showing windows for X+ and X− where they are not clamped (betweenVmax=3.9 and Vmin=0.6), and showing a window where they are suitable forsensing (greater than Vsl=0.7). Note that the sensing window iseffectively capped at Vmax, because V+ and V− cannot exceed this value.

Note that the magnitude of Vsl, and perhaps operation of the comparators154+ and 154−, could depend on the manner in which the differentialamplifier 111 is built. For example, if transistors M+ and M− in thedifferential amplifier 111 are PMOS transistors, Vsl could insteadcomprise a high sense reference voltage Vsh (e.g., Vdd−Vtt) that isprovided to negative inputs of the comparators 154+ and 154−, with X+and X− being provided to positive inputs of the comparators. If X+ or X−are below Vsh as would be necessary for proper differential amplifier111 operation in this circumstance, the comparators 154+ or 154− wouldoutput a ‘0’, and En=‘0’, indicating to the ECAP algorithm 124 thatECAPs can be reliably sensed. If either of X+ or X− were above Vsh,En=‘1’, indicating the opposite.

FIGS. 7A and 7B describe a second example of a sense amp circuit 210.Sense amp circuit 210 is similar to sense amp circuit 200, and includesclamp circuits 142+ and 142− and DC-level shifting circuits 143+ and143− as described earlier. However, the comparators circuitries 150+ and150− include additional comparators 152+ and 152− respectively. Whilecomparators 154+ and 154− are designed to inform when X+ and X− are toolow for valid ECAP sensing, comparators 152+ and 152− are designed toinform when X+ and X− are too high for valid ECAP sensing. In thisregard, even though the clamp circuits 142+ and 142− would clamp X+ andX− to a maximum voltage Vmax (e.g., 3.9V), it may still be desirable toenable ECAP sensing only if X+ and X− are below this maximum. As notedearlier, high values for X+ and X− can also adversely affectdifferential amplifier 111 operation, even if such high values do notrisk damaging the amplifier. Furthermore, ECAP sensing will not bereliable if X+ and X− are significantly high to cause diodes 144 b inthe clamp circuits 142+ and 142− to conduct.

In this regard, X+ and X− are sent to the positive inputs of comparators152+ and 152−. The negative inputs are provided a high sense referencevoltage Vsh. Like Vsl, Vsh can be set to different values (using agenerator circuit like 141), but in a preferred example, Vsh is set tothe power supply voltage Vdd (e.g., 3.3V). In this manner, comparators152+ and 152− respectively output a ‘1’ if X+ or X− are greater thanVsh. In comparator circuitry 150+, the outputs of comparators 152+ and154+ are provided to logic circuitry such an OR gate 156+, which outputssignal Y+. Likewise, in comparator circuitry 150−, the outputs ofcomparators 152− and 154− are provided to an OR gate 156−, which outputssignal Y−. Signal Y+ informs whether X+ is too high (‘1’), too low(‘1’), or suitable for ECAP sensing (‘0’), and signal Y− similarlyinforms whether X− is too high (‘1’), too low (‘1’), or suitable forECAP sensing (‘0’). As in circuit 200 (FIG. 6A), these outputs Y+ and Y−are provided to an OR gate 158 to produce the enable signal En for ECAPsensing. FIG. 7B summarizes operation of the sense amp circuit 210,showing windows for X+ and X− where they are not clamped (betweenVmax=3.9 and Vmin=0.6), and showing a window where they are suitable forsensing (between Vsl=0.7 and Vsh=3.3V). The sense amp circuit 210 ispreferred because the sensing window is smaller than and within thewindow where clamping does not occur. This way, ECAP sensing is disabled(En=‘1’) before the X+ or X− becomes too large or too small to beclamped by their clamp circuits 142+ and 142−.

Comparator circuitries 150+ and 150− need not necessarily comprisediscrete comparators such as 152+, 152−, 154+, and 154+. Instead,comparator circuitries 150+ and 150− may include Analog-to-Digitalconverters (ADCs) to produce digital representations of X+ and X−, whichmay comprise discrete circuits, or which may comprise ADC inputs of thecontrol circuitry 102. The digitized values for X+ and X− may then bedigitally compared (e.g., in the control circuitry 102) to variousthresholds to determine whether they meet the input requirements of thedifferential amplifier 111, e.g., to see if X+ and X− are each betweenVsl and Vsh. The result of these determinations can be expressed as adigital signals Y+ and Y− (e.g., again in the control circuitry 102),which are used by logic circuitry (e.g., again in the control circuitry102) to determine the enable signal, En. In this regard, note thatcomparator circuities 150+ and 150− may be formed, at least in part, inthe control circuitry 102 or using other digital logic circuits.

FIG. 8 shows another example of a sense amp circuit 220. As with otherexamples, sense amp circuit 220 includes clamp circuits 142+ and 142− toclamp X+ and X− to a maximum (Vmax) and preferably also minimum (Vmin)values. However, in sense amp circuit 220, whether ECAP sensing isindicated, and the value of enable signal En, is set by comparatorcircuitry 166 that differs compared to comparator circuitries 150+ and150− described earlier. Instead, in sense amp circuit 220, comparatorcircuitry 166 effectively measures the current I+ and I− in each leg ofthe differential amplifier 111 to ensure that both legs are producingsuitable currents indicative of proper amplifier operation.

As noted earlier, the differential amplifier 111 can only operate tosense ECAPs if both transistors M+ and M− are on to produce significantcurrents I+ and I− in their legs. In this regard, differential amplifieroutputs D+ and D− may be assessed by comparator circuitry 166 to verifywhether such currents are flowing. In the example of differentialamplifier 111, leg currents I+ and I− flow through resistors R+ and R−,such that D+ equals Vdd−(I+*R+) and D− equals Vdd−(I−*R−). D+ and D− aretherefore lower if significant currents I+ and I− are flowing. If thesecurrents are too small or insignificant, D+ and D− will be too high.

Accordingly, comparator circuitry 166 can include comparators 168+ and168− to gauge the magnitude of differential outputs D+ and D−, which asjust noted are indicative of the currents I+ and I− flowing through thedifferential amplifier's legs and hence compliance with the amplifier'sinput requirements. Comparator 168+ receives D+ at its positive input,while comparator 168− receives D− at its positive input. The negativeinputs of both comparators 168+ and 168− are set to a reference voltage,Vref, by a generator circuit 161. Again, generator circuit can takedifferent forms, but is shown in FIG. 8 as an adjustable current inseries with a resistance R. Vref is preferably just slightly below powersupply voltage Vdd, such as 150 mV less than Vdd. These outputs Y+ andY− can be sent to an OR gate 170 to produce the enable signal En thatinforms the ECAP algorithm 124 whether the ECAP signal present at output145 is valid for ECAP sensing. If both of I+ or I− in the differentialamplifier 111 are significant (because X+ and X− are significantlyhigh), both of D+ or D− will be lower than Vref, and both of comparators168+ or 168− will output a ‘0’ for Y+ and Y−. OR gate 170 in turnoutputs the enable signal En as a ‘0’, indicating that the ECAP atoutput 145 is valid to sense. By contrast, if either or both of I+ or I−in the differential amplifier 111 are too small (because either or bothof X+ or X− are too low), either or both of D+ or D− will be higher thanVref, and either or both of comparators 168+ or 168− will output a ‘1’.OR gate 170 in turn outputs the enable signal En as a ‘1’, indicating tothe ECAP algorithm 124 that the output 145 does not carry a valid andreliable ECAP signal, and hence that the output 145 should be ignored.

Comparator circuitry 166, like 150+ and 150−, need not necessarilycomprise discrete comparators such as 168+ and 168−. Comparatorcircuitry 166 may include Analog-to-Digital converters (ADCs) to producedigital representations of D+ and D−, which may comprise discretecircuits, or which may comprise ADC inputs of the control circuitry 102.The digitized values for D+ and D− may then be digitally compared (e.g.,in the control circuitry 102) to Vref. The result of thesedeterminations can be expressed as a digital signals Y+ and Y− (e.g.,again in the control circuitry 102), which are used by logic circuitry(e.g., again in the control circuitry 102) as above to determine theenable signal, En. Thus, as with comparator circuitries 150+ and 150−,comparator circuitry 166 may be formed, at least in part, in the controlcircuitry 102 or using other digital logic circuits.

As in other examples, the sense amp circuitry 220 may be modifieddepending on the type of differential amplifier 111 that is used.

The various examples of the sense amp circuits can also be combined invarious ways. For example, FIG. 9 shows a sense amp circuit 230 thatcomprises a combination of the approaches used in sense amp circuit 210(FIG. 7A) and sense amp circuit 220 (FIG. 8). As in circuit 220,comparators 168+ and 168− are used as part of comparator circuitries175+ and 175−, and assess the outputs D+ and D− of the differentialamplifiers 111 by comparison to Vref to inform whether inputs X+ and X−to the differential amplifier 111 are too small to turn on both of theamplifier's legs. In this respect, comparators 168+ and 168− essentiallytake the place of comparators 154+ and 154− in FIG. 7A. Comparators 152+and 152− are used as before to assess inputs X+ and X− to ensure thatthey are not too large. The outputs of the comparators in each circuit150+ and 150+ can again be logically ORed (156+ and 156−) to generatesignals Y+ and Y−, with these signals in turn being ORed (158) toproduce the enable signal, En.

When sensing tissue signals such as ECAPs, it is preferred that thesense amp circuits be used in a differential mode in which each input X+and X− is coupleable to electrodes in contact with the patient's tissue.As noted earlier, this is desirable to try at the differential amplifierto subtract the stimulation artifact 134 as a common mode voltage, thusmaking it easier to sense the small-signal ECAPs.

However, this is not strictly necessary, and the disclosed sense ampcircuits could instead be used in a single-ended mode in which one ofthe amplifier inputs (e.g., X−) is set to a reference voltage, Vamp, asshown in FIGS. 10A and 10B. Such reference voltage can be a DC voltagesuch as 1/2 Vdd, 2.0 V, and should be high enough to turn on inputtransistor M− of the differential amplifier 111. Single-ended sensingcan be useful to sense other signals at the electrodes, such as thestimulation artifact 134 itself.

FIG. 10A shows a single-ended sense amp circuit 240 which is similar tosense amp circuit 210 (FIG. 7A) shown earlier. Because X− is set toVamp, comparator circuitry 150−, clamp circuit 142− and DC-levelshifting circuit 143− are unnecessary, and thus are not shown. Inreality, these circuits may still be present in sense amp circuit 240,but would simply be disabled or disconnected from the circuit when Vampis selected (see multiplexer 108, FIG. 4) as the reference at input X−.Notice in this example that signal Y+ can operate as the enable signalthat determines whether input X+ is valid, and that OR gate 158 (FIG. 4)is unnecessary.

FIG. 10B shows a single-ended sense amp circuit 250 which is similar tosense amp circuit 220 (FIG. 8) shown earlier. Because X− is set to Vamp,clamp circuit 142− and DC-level shifting circuit 143− are unnecessary,and could be disabled or disconnected. Likewise, in comparator circuitry166, comparator 168− would be unnecessary (or disabled/disconnected),and again signal Y+ can operate as the enable signal, En.

As noted earlier, an ECAP is just one example of a neural response thatcan be sensed using the disclosed sense amp circuits. Not all neuralresponses one might desire to sense are a result of stimulation, and inthis regard the disclosed sense amp circuits can be used in animplantable device that may not include stimulation circuitry 28 (FIG.4). Furthermore, the disclosed sense amp circuits can be used to senseother types of signals in the tissue beyond neural responses. Forexample, the sense amp circuitry could be used to sense other types ofsignals, such as those used for measuring tissue field potentials ortissue resistance.

Although particular embodiments of the present invention have been shownand described, the above discussion is not intended to limit the presentinvention to these embodiments. It will be obvious to those skilled inthe art that various changes and modifications may be made withoutdeparting from the spirit and scope of the present invention. Thus, thepresent invention is intended to cover alternatives, modifications, andequivalents that may fall within the spirit and scope of the presentinvention as defined by the claims.

What is claimed is:
 1. An implantable medical device, comprising: afirst electrode node coupleable to a first electrode configured to makeelectrical contact with a patient's tissue, and a second electrode nodecoupleable to a second electrode configured to make electrical contactwith the patient's tissue, wherein the first electrode node isconfigured to receive via the first electrode a tissue signal from thepatient's tissue; an amplifier with a first input connected to the firstelectrode node and with a second input connected to the second electrodenode, wherein the amplifier produces an amplifier output indicative ofthe tissue signal; first comparator circuitry configured to receive thefirst input and to generate a first output indicating whether the firstinput meets an input requirement of the amplifier; second comparatorcircuitry configured to receive the second input and to generate asecond output indicating whether the second input meets an inputrequirement of the amplifier; and first logic circuitry configured toreceive the first output and the second output and to generate an enablesignal, wherein the enable signal indicates whether the amplifier outputindicative of the tissue signal is valid or invalid.
 2. The implantablemedical device of claim 1, wherein the first and second electrode nodescomprise two of a plurality of electrodes nodes, and wherein the firstand second electrodes comprise two of a plurality of electrodes, whereineach of the plurality of electrode nodes are coupleable to a differentone the plurality of electrodes, wherein the plurality of electrodes areconfigured to make electrical contact with the patient's tissue.
 3. Theimplantable medical device of claim 2, further comprising a selectorcircuit configured to select the first and second electrode nodes fromthe plurality of electrode nodes.
 4. The implantable medical device ofclaim 2, further comprising stimulation circuitry configured to producestimulation in the tissue via selected ones of the plurality ofelectrodes, wherein the tissue signal is generated in the patient'stissue in response to the stimulation.
 5. The implantable medical deviceof claim 1, wherein the second electrode comprises a conductive case ofthe implantable medical device.
 6. The implantable medical device ofclaim 1, further comprising a lead, wherein the lead comprises the firstand second electrodes.
 7. The implantable medical device of claim 1,wherein a first blocking capacitor intervenes between the firstelectrode node and the first electrode, and wherein a second blockingcapacitor intervenes between the second electrode node and the secondelectrode.
 8. The implantable medical device of claim 1, wherein thetissue signal comprises a neural response.
 9. The implantable medicaldevice of claim 1, further comprising a first clamping circuitconfigured to keep a voltage at the first input from exceeding a firstvalue, and a second clamping circuit configured to keep a voltage at thesecond input from exceeding the first value.
 10. The implantable medicaldevice of claim 9, wherein the first clamping circuit is furtherconfigured to keep the voltage at the first input from going below asecond value, and wherein the second clamping circuit is furtherconfigured to keep the voltage at the second input from going below thesecond value.
 11. The implantable medical device of claim 1, furthercomprising a first DC-level shifting circuit configured to set a DCvoltage reference at the first input, and a second DC-level shiftingcircuit configured to set the DC voltage reference at the second input.12. The implantable medical device of claim 1, wherein the amplifiercomprises a first input transistor with a first control terminal forreceiving the first input, and a second input transistor with a secondcontrol terminal for receiving the second input, wherein the first andsecond input transistors comprise a threshold voltage that mustrespectively be exceeded at the first and second inputs to turn on thefirst and second transistors.
 13. The implantable medical device ofclaim 12, wherein the first comparator circuitry comprises a firstcomparator configured to indicate at the first output whether a voltageat the first input exceeds the threshold voltage, and wherein the secondcomparator circuitry comprises a second comparator configured toindicate at the second output whether a voltage at the second inputexceeds the threshold voltage.
 14. The implantable medical device ofclaim 1, wherein the first comparator circuitry comprises: a firstcomparator configured to indicate whether a voltage at the first inputexceeds a first voltage, a second comparator configured to indicatewhether the voltage at the first input is below a second voltage, andsecond logic circuitry configured to receive the outputs of the firstand second comparators and to generate the first output, wherein thefirst output indicates whether or not the voltage at the first input isbetween the first and second voltages; and wherein the second comparatorcircuitry comprises: a third comparator configured to indicate whether avoltage at the second input exceeds the first voltage, a fourthcomparator configured to indicate whether the voltage at the secondinput is below the second voltage, and second logic circuitry configuredto receive the outputs of the third and fourth comparators and togenerate the second output, wherein the second output indicates whetheror not the voltage at the second input is between the first and secondvoltages.
 15. The implantable medical device of claim 14, wherein thefirst voltage comprises a threshold voltage of input transistors in theamplifiers, and wherein the second voltage comprises a power supplyvoltage of the amplifier.
 16. The implantable medical device of claim 1,further comprising control circuitry configured to receive the amplifieroutput indicative of the tissue signal, wherein the control circuitry isprogrammed with an algorithm configured to analyze the amplifier output,wherein operation of the algorithm is controlled by the enable signal.17. An implantable medical device, comprising: a first electrode nodecoupleable to a first electrode configured to make electrical contactwith a patient's tissue, wherein the first electrode node is configuredto receive via the first electrode a tissue signal from the patient'stissue; an amplifier with a first input connected to the first electrodenode and with a second input connectable to a reference voltage, whereinthe amplifier produces an amplifier output indicative of the tissuesignal; and comparator circuitry configured to receive the first inputand to generate an enable signal indicating whether the first inputmeets an input requirement of the amplifier, wherein the enable signalindicates whether the amplifier output indicative of the tissue signalis valid or invalid.
 18. The implantable medical device of claim 17,wherein the first electrode node comprises one of a plurality ofelectrodes nodes, wherein each of the plurality of electrode nodes arecoupleable to a different one the plurality of electrodes, wherein theplurality of electrodes are configured to make electrical contact withthe patient's tissue, further comprising a selector circuit configuredto select the first electrode nodes from the plurality of electrodenodes.
 19. The implantable medical device of claim 17, wherein thereference voltage comprises a DC voltage.
 20. The implantable medicaldevice of claim 17, wherein the tissue signal comprises a neuralresponse.